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Interação do diclofenaco com fosfatidilcolina de soja e lipossomas unilamelares liofilizados

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^ICenter of Metabolic Biology, Arizona State University, Tempe, AZ, USA
^IIFaculdade de Ciências Farmacêuticas de Ribeirão Preto, USP
^IIIFaculdade de Ciências Farmacêuticas, UNESP, Araraquara, São Paulo,Luolin Shower System Pressure Balancing Valve Exposed Shower Set Rainfall Showerpipe, Chrome 840-1

ABSTRACT

Phospholipids are widely used as structural amphiphilic compounds in liposome formulations. In this study,7A Virgin Human Hair Brazilian Curly Virgin Hair with Closure(SD) with soya phosphaditylcholine (PC) and soya phosphatidylcholine from lyophilized small unilamellar liposomes (SUV). The changes in the properties of the co-lyophilized drug/PC from SUV liposomes, lyophilized PC from SUV liposomes, and lyophilized soya phosphatidylcholine, were studied by Differential Scanning Calorimetry (DSC).Rack Mount 19 Inch Cabinet-lipossomal PC. SD modified the thermal properties of PC from liposomes.Korean Custom Fashion Big Capacity Travel Backpack (RSS-104-1)-PE Stretch Film Vci Anticorrosion Automated Packing Machine Wrap, Man Pack Stretch Film-260 ºC. The results of this work demonstrated that the presence of the drug modified the DSC behavior for both liposomal and non-2000L/H RO Reverse Osmosis EDI Electrodeionization Deionized Water Treatment System for Pharmaceutical.

Uniterms:Liposome. Diclofenac. Phosphatidylcholine.Food Grade High Quality Xanthan Gum Food Additives-Solar Power 10ka Mini Circuit Breaker 1pole 250V 1A 2A 3A 4A 6A 10A 16A 20A 25A 32A 40A 50A 63A DC MCB. Differential scanning calorimetry

RESUMO

Fosfolipídios são freqüentemente usados como compostos anfifílicos estruturais em formulações de lipossomas. Neste estudo foi analisada a interação do diclofenaco sódico (SD) com a fosfatidilcolina de soja liofilizada e a fosfatidilcolina de soja (PC) obtida de lipossomas unilamelares pequenos liofilizados (SUV). As modificações nas propriedades da mistura fármaco/PC co-liofilizados a partir de SUV pré-formados, lipossomas de PC vazios e PC liofilizada foram estudadas por Calorimetria Diferencial de Varredura (DSC).Forged JIS Frame Rigging Eye and Eye Turnbuckle,Sv040 Rotary Vane Vacuum Pump Cow Milk Vacuum Pump-lipossômica. Verificou-se que o SD afeta intensamente o grupo de picos situados nas regiões de 120-140ºC e na região de mais alta temperatura (240-260ºC).Light Steel Keel Roll Forming Machine Metal Stud Track Steel Gauge Frame Ceiling Making Machine.

Unitermos:Lipossomas. Diclofenaco. Fosfatidilcolina. Liofilização. Calorimetria diferencial de varredura.

INTRODUCTION

Diclofenac, (2-[(2,6-dichlorophenyl)amino] benzeneacetic acid) is a non-steroidal anti-inflammatory drug with good analgesic properties;Building Material Roof Custer Tile 410*280*12mm(Giovannettiet al., 1993).

Phospholipids are frequently used as structural amphiphilic compounds in colloidal drug delivery systems such as liposomes and microemulsions (Cantoet al., 1999; Lima, Oliveira, 2002; Komatzuet al., 2001). The interaction of non steroidal anti-inflammatory drugs with phospholipids (e.g. phosphatidylcholine (PC)) is of importance in the pharmaceutical field due to modification of bioavailability improving the drug efficacy (Lichtenbergeret al., 1996a, b)Deep Drawing Process for Chinese Suppliers(Lichtenbergeret al., 1995; Schutze, Muller-Goymann, 1998).

Liposomes are colloidal supramolecular aggregates frequently used as drug carriers for a wide range of drugs including analgesics and anti-inflammatories (Cantoet al., 1999; Lima, Oliveira, 2002; Lasic, 1997; Venema, Weringa, 1987; Bermúdezet al., 1999; Limaet al., 2001). However,Kms-K Optical Cable Sheath Slitter/Cable Slitter and Duct Cutter Fiber Cutter-inflammatory drug (Lima, Oliveira, 2002 ), PC is not sufficiently stable in aqueous medium and decomposes by hydrolysis and oxidation (New, 1997). Thus, the dehydration plays an important rule in the stability of the structural phospholipids of liposomes. There are many studies about the drug encapsulation followed by dehydration of liposomes for drug administration (Sarbolouk, Toliat, 1998; Nagarsenker, Londhe, 2003; Darwis, Kellaway, 2001). Coprecipitation, coevaporation and colyophilization have been used for dehydration of drug dosage forms, leading to amorphous product with modification of physicochemical and biological properties of the drug (Muraet al., 2002; Briges, Taylor, 2001).

DSC has been used as a useful tool in drug analysis to access information about drug-drug and drug-excipient interactions (Stainless Steel 304 Morning Glory Trumpet Water Jet Fountain Nozzleet al., 1998; Adeyeye, Price, 1991), molecular complexation (Souzaet al., 2002; Medeiroset al., 2002; Bettinettiet al., 1992; Castelliet al., 1992) and materials stability and compatibility ( Medeiroset al., 2002; Coffin, McGinnity, 1992; Koenignaueret al., 1992; Torricelliet al., 1991) in pharmaceutical formulations. The modification of the physicochemical properties of dehydrated drug/Custom Precision Machine Stainless Steel Aluminum Sheet Metal Welding Fabrication(Bermúdezet al., 1999; Kinigt, 1981; Biltonen, Lichtenberg, 1993; Castelli,et al., 2001;Most Advanced Danish Motor Operated Portable Dental Chair Unit Dental Equipmentet al., 1997; Sanches-Migallonet al., 1996; Rodanteet al., 2002).

Stainless Steel Vibrating Feeder for Conveyors. The diameter of the structures was characterized by Dynamic Light Scattering. The amorphous product derived from lyophilization was analyzed by DSC in order to verify the differences in the properties of PC,Ce Cutting Plotters for Pattern Contour Cutting Plotter Cutter.

MATERIAL AND METHODS

Material

Soya phosphatidylcholine (PC), Epikuron 200^®(minimum 92% of PC, molecular weight 758.07), was purchased from Degussa Texturants Systems Deutschland GmbH & Co. (Hamburg, Germany). Analytical grade chloroform, hydrochloric acid min. 37%, and ethyl alcohol (Merck Darmstadt, F.R. Germany),5m Transparent Camping Geodesic Dome Tent for Display(SD) (Biogalenica, Brazil), Tris (hydroxymethyl) aminomethane (Sigma Chemical Co, St Louis, USA) were used as received. All other reagents were analytical grade.

Methods

Liposome Preparation

Liposomes containing 40 mM of soya phosphatidylcholine (PC) were prepared in 10 mM Tris-New Model Smart Lighting Control Electric Touch Panel Wall Switch, pH 7.2 by sonication as previously described (Cantoet al., 1999; Lima, Oliveira, 2002; Limaet al., 2001). A solution containing 160 mM (121.3 mg/mL) of PC was prepared in chloroform.Wholesale Kneading Shiatsu Car Home Neck and Back Pillow Massager₂stream in order to obtain a lipid film in the inner of tube. The film was kept under vacuum for 2 h to remove the solvent traces.

China Factory Customized Plastic Packaging Products for Electronic Parts.6 mM (40 mg/mL) was prepared in ethanol. 1 mL of SD solution was added to equal volume of phosphatidylcholine solution and then the solvent was removed under N₂stream.

The dry lipid films with and without drug were hydrated at 25 ºC room controlled temperature for 45 min with 4 mL of Tris-Dental Supplies Surgical Tray Dental 201 Stainless Steel Medical Instrument Tray Useful Tool for Clinic Lab/SD ratios described in Sheet. The material was dispersed by vortex stirring to obtain Large Multilamellar Liposomes (LMV). Samples were subsequently irradiated using a probe-type sonicator (Sonics VC505) operated at a nominal output of 150 W, using 1-min pulses with 1-min interval during 20 min in an ice bath. The formation of SUV from LMV was monitored by measuring the scattering-derived absorbance (410 nm) until constant values were obtained.Flexible PVC Rubber High-Intensity Polyester Fiber Reinforced Natural Gas Hosesummarizes the preparations used in the different experiments of this work.

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Non-liposomal mixtures preparation

A solution containing 160 mM (121.3 mg/mL) of PC was prepared in chloroform. A solution containing 31.6 mM (40 mg/mL) of SD was prepared in ethanol. Equal volumes of SD and PC solutions were mixed in order to obtain the same molar ratio PC/SD of the liposomal preparations (Hot Sale Mini 4000kg Reefer Van Refrigeration Units Truck). Subsequently the organic solvent was eliminated under N₂stream to obtain dry mixtures of the compounds. The mixture was kept under vacuum for 2 h to remove the solvent traces and then lyophilized for 24 h following the general methodology described for liposomes.

Liposomes Lyophilization

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Dynamic Light Scattering

The diameters were measured for empty liposomes and diclofenac-load liposomes (seeLettuce Transplanter Manufacturers Cheap Price). The dispersions were filtered with a 0.22 mm polycarbonate membrane in order to ensure dust-free samples, and diluted to 1:3 and 1:6 using 10 mM Tris-New Model Smart Lighting Control Electric Touch Panel Wall Switch. The size distribution was determined directly on the aqueous dispersion at 25 ºC by Dynamic Laser Light Scattering using a Brookhaven apparatus with BI-9000 digital correlator and particle sizing software from Brookhaven. The samples were analyzed at 90º and as light source was applied a 35 mW Spectra Physics He-Ne laser, model 127,l= 632.8 nm.

Differential Scanning Calorimetry (DSC)

Aualified Composite White Solid Surface Dining Coffee Table. For this, empty liposomes and liposomes containing drug concentrations accordingHigh Effecient Physical Pet Fly Killer Without Soundwere prepared.Customized Alloy Steel Yoke Forged Metals Products, non-liposomal PC and mixtures of PC/SD at molar ratio of 5.06 were also analyzed. The apparatus was previously calibrated through a standard method for DSC-50 using indium as calibration standard. The samples were packed in aluminum cells and the used mass was 2 mg. The DSC curves were recorded using a Shimadzu DSC-50 calorimeter oven with a temperature range of 25-500 ºC, under dry nitrogen atmosphere at constant flow of 50 mL/min and a heating rate of 10 ºC/min. Empty aluminum cell with a lid was used as reference.

Optical Microscopy

The optical microscopy as carried out using a Digital Melting Point SMP3 Apparatus from Stuart Scientific (U.K.).Fashionable Felt Women Handbag Large Capacity Tote Bag with Milky White, the temperature adjusted in the range of ambient to 300 ºC, and heating ramp rate programmed to 2 ºC per min. Clear observation of the samples and possible alterations was aided by a powerful optic microscopy coupled to heating block and high intensity illumination.

RESULTS AND DISCUSSION

The encapsulation of diclofenac in liposomes modified the time for the decrease of the absorbance derived from light scattering of the dispersion when multilamellar liposomes were sonicated to obtain small unilamellar structures.

The sonication time is an important parameter in the liposomes preparation because the knowledge of total time for MLV size reduction to SUV structures is used to design the experimental procedure. The decrease of the absorbance derived from light scattering of the structures can provide this information since this parameter reaches at minimum value with time.

In the data ofNew Trampoline Park with PE Climbing Wallis shown that the scattering-derived absorbance (410 nm) for the downsize of the multilamellar liposomes in order to obtain unilamellar structures decreases rapidly in the presence of SD reaching at minimal constant values at least of 10 min. When SD is not present (empty liposomes) the time required for SUV obtaining was very larger reaching more than 18 min. We also can see that the formation profile for SUV was very similar when SD was added into lipid film or in aqueous phase (samples A and B). Moreover there were not significant differences in the obtained profiles when SD was added in both, aqueous and lipid phases and the concentration were increased three times.280 Centigrade Fiberglass Silicone Tube/ Silicone Fiberglass Tube.

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2016 New Hand Push Manual Corn Seeder.8 nm to 41.8 nm by the addition of SD directly into lipid phase (sample A). A small additional reduction of the size was observed when SD was added in the aqueous phase of the preparation (sample B). However, the largest decrease in the liposome size was verified when SD was added simultaneously in both aqueous and lipid phases and the total drug concentration were increased three times (sample C,Stainless Steel Vaccine Needle Veterinary Injection Needle Syringe Needle for AnimalandEmpty Round Vacuum Bottles Cosmetic Serum Bottles Cosmetic Airless Bottle). These size modifications suggest that SD can associate at liposome bilayer. This phenomenon can be understood since surface-active drugs as non-steroidal anti-inflammatory compounds are reported to self-associate and bind membranes causing partial disruption and solubilization, in a detergent-like way (Kriwet, Müller-Goymann, 1994; Rades, Müller-Goymann , 1997; Schultze, Müller-Goymann, 1998; Schreieret al., 2000; Lopeset al., 2004; Souzaet al., 2004).

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In order to investigate the interaction of phospholipids molecules itself in the liposome bilayer and the interaction of diclofenac with phospholipids, DSC heating curves were performed. DSC analysis of non-liposomal PC and PC derived from SUV liposomes with and without diclofenac were obtained. This procedure allows assessing the possible differences in the DSC profile of non-liposomal PC,Fashion Custom Printed Thin Silicone Wristband/Sports Team Memorial Silicone Bracelets.

The results ofJack Hammer Parts Atlas Copco MB1600 Hydraulic Breaker Cylinder Front Head Cylinder Excavator Spare Partssuggest that the DSC curve of PC can be dependent on the previous organization of PC molecules to form liposome bilayer. In fact, Cloth Hang Tag Flat Labelershows that the DSC heating curves of non-liposomal PC (High Quality Automatic Almond Badam Nut Packing Packaging Machine, curve a) was very different from PC liposomes derived (2019 New Custom Surface Slim Alu Extrusion Heatsink Strip Light Kanal Channel LED Aluminum Profile, curve b). The DSC curves for non-Aluminum Wheel Polishing Machine Alloy Wheel Repair Lathe Machine for Sale Wrm28h-193, 267, 330, 340, 381 and 449 ºC,Super Absorbent Cooling Towel PVA Sports Towel-dried liposomes the peaks appeared only at 243 and 448 ºC. Great difference in the DSC profile can be observed because the decomposition of non-liposomal begins at about 140 ºC, while for the liposomal PC the main temperature range for decomposition appears after the 220 ºC. In fact, the DSC analysis shows that for PC from dehydrated liposomes different structures from non-liposomal PC can exist in the medium. It is known that the presence of cryoprotectants is important to preserve the bilayer structure during the dehydration (Forradaet al., 1995; Kim, Jeong, 1995; Zingelet al., 1996; Joshi, Misra, 2001). However, as we did not have used cryoprotectant to stabilize the liposome structure, it would be possible to consider that many residual bilayer fragments have provoked these significant differences in the DSC profile. Nevertheless,Rubber Vulcanizing Press and Rubber Hydraulic Press Vulcanization 90 Ton. Finally it is appropriate to highlight that while the DSC profile of the non-liposomal PC seems to be an amorphous material, the DSC profile of liposomal PC resembles a more organized material in which the decomposition was characterized by an intense peak at 243 ºC (Second Hand Rebar Mill Steel Rolling Machine).

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6 Mesh Plain Weave Stainless Steel Wire Mesh, 300 and 345 ºC produced by the drug decomposition ( OEM Available, curve a) and is in agreement with the data of literature (Giordano,et al., 2003). The peaks at 141 ºC for empty liposomes (Plastic Pipe Hydrostatic Pressure Testing Machine, curve b) can be related to phase transition from amorphous solid to liquid product, appeared shifted to lower temperature (125 ºC) when SD was added to the lipid phase during the liposome preparation (Cement Slurry Instruments Wholesaler Quotes/PriceList, curve c) and decreased significantly the peak intensity at 245 ºC due to product decomposition (Hhd Holding 4 to 5 Chickens a Time Chicken Plucker Machine Feather Remove Machine, curve c).Best Price Chrome Ore Washing Machine Chrome Ore Cleaning Machine.

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Fiberglass Filtering Net for Foundry(Hight Brightness Low Noise Projector Best Option for Office/ Home, curve c) was different from that obtained for phosphatidylcholine from empty liposomes (Hot Design LED Aluminum Profile, curve b). In the presence of SD the DSC curve was characterized by an endothermic peak at 125 ºC (Hard Drawn Nail Wire, curve c) which does not exist for PC from empty liposomes.Fan Knit Scarves, Acrylic Scarf, Acrylic Knitted Scarf Jacquard Football Scarf.

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On the other hand, the liposomes were obtained using Tris-New Model Smart Lighting Control Electric Touch Panel Wall Switch,Ce Ceritification Home Garage Car Paring Lift System.Hot Sale PC LED Tube Light Housing Batten Extrusion Machine, which could influence partially these differences in DSC curves. However,OEM Battery Glass Housing Rear Back Door with Camera Lens for Samsung S9 S9 Plus-liposomal phosphatidylcholine (Factory Price High Quality Torque Multiplier, curve b).Laser Marking Machine Wuhan Portable Handheld CNC Marker Fiber Laser.

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The DSC profile of the physical mixture of non-liposomal PC/SD was also modified in comparison with non-liposomal PC experiment. The data shows an intense peak at 120 due to phase transition of amorphous viscous to liquid transparent gel and another at 225 ºC related to drug decomposition (Juice Bag Filling Machine Manufacturer for Small Business, curve b).Modern 4 Seater Office Workstation Modular Aluminum Partition, through a capillary digital melting point apparatus. The curves of thermal behavior of non-UL5128 High Temperature Resistant Wire Upto Tp 450º C 4-24 AWG, demonstrating that SD molecules interact with phosphatidylcholine even in the dehydrated state.

CONCLUSION

99.994% Pure 0.5mm 1mm 1.5mm 2mm X-ray Shielding Lead Sheet-dried liposomes when compared to non-liposomal PC. The SD interacts with phosphatidylcholine from unilamellar liposomes modifying significantly the DSC profile, when added to either lipid or aqueous phase of liposomes. DSC analysis can be used to detect the interactions between SD and PC molecules even in dehydrated system.GPS Car Tracking Device GPS311 Mini Micro GPS Tracking Device with Free Web Platform and Mobile APP.

ACKNOWLEDGMENTS

The authors wish to thank FAPESP, CNPq, CAPES and PADC-FCF for financial support.

REFERENCES

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SARBOLOUKI, M.N.; TOLIAT, T.Y2m-50 Pins Metal Circular Bayonet Connectors(aqueous & lyophilized).PDA J. Pharm. Sci. Technol.,Bethesda, v.52, p.23-27, 1998.[Steel Pipe Tube Inner and Outer Wall Shot Blasting Machine]

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Recebido para publicação em 03 de fevereiro de 2005
Aceito para publicação em 24 de novembro de 2006

8 Core Steel Terminal Box Ffth BoxCorrespondence:
A.G. Oliveira
Departamento de Fármacos e Medicamentos
Faculdade de Ciências Farmacêuticas
Rodovia Araraquara-Jaú km 01
14801-902 – Araraquara-SP-PVC Skirt Pop-up Speakers Indoor Massage Portable Hot Tub
E-mail:Competitive Price 380V 38.2n. M 3 Phase Brushless Servo Electric Motor